Third seed Jessica Pegula left the court in tears after a frustrating US Open fourth-round defeat by American compatriot Madison Keys.
Pegula had been one of the favourites for the title but put in a poor performance in a 6-1 6-3 defeat.
Despite her success on the WTA Tour, the 29-year-old has yet to go beyond the quarter-finals at any Grand Slam.
Keys, runner-up in New York in 2017, will face Wimbledon champion Marketa Vondrousova next.
Pegula won the Canadian Open in the build-up to the final major of the year, registering a notable victory over top ranked Iga Swiatek in the process.
However, she has consistently struggled to break through at the majors, having never gone beyond the last eight in six attempts.
Pegula was off-colour from the start, struggling to find her rhythm against the big-hitting Keys.
She hit just three winners in the first set, which she lost in just 28 minutes, and quickly found herself a break down in the second.
Pegula was able to take advantage of a blip from Keys to retrieve the break for 3-3, but she lost the next three games as Keys reasserted her dominance.
The two are good friends, having often trained together, and shared a warm hug at the net before a tearful Pegula left the court.
Keys will now face Vondrousova, who had to fight back to see off spirited American Peyton Stearns 6-7 (3-7) 6-3 6-2.
It is the first time the Czech has reached the quarter-finals in New York.